Degenerative Damage Research Articles

Effects of Adult Müller Cells and Their Conditioned Media on the Survival of Stem Cell-Derived Retinal Ganglion Cells.

Retinal neurons, particularly retinal ganglion cells (RGCs), are susceptible to the degenerative damage caused by different inherited conditions and environmental insults, leading to irreversible vision loss and, ultimately, blindness. Numerous strategies are being tested in different models of degeneration to restore vision and, in recent years, stem cell technologies have offered novel avenues to obtain donor cells for replacement therapies. To date, stem cell–based transplantation in the retina has been attempted as treatment for photoreceptor degeneration, but the same tools could potentially be applied to other retinal cell types, including RGCs. However, RGC-like cells are not an abundant cell type in stem cell–derived cultures and, often, these cells degenerate over time in vitro. To overcome this limitation, we have taken advantage of the neuroprotective properties of Müller glia (one of the main glial cell types in the retina) and we have examined whether Müller glia and the factors they secrete could promote RGC-like cell survival in organoid cultures. Accordingly, stem cell-derived RGC-like cells were co-cultured with adult Müller cells or Müller cell-conditioned media was added to the cultures. Remarkably, RGC-like cell survival was substantially enhanced in both culture conditions, and we also observed a significant increase in their neurite length. Interestingly, Atoh7, a transcription factor required for RGC development, was up-regulated in stem cell-derived organoids exposed to conditioned media, suggesting that Müller cells may also enhance the survival of retinal progenitors and/or postmitotic precursor cells. In conclusion, Müller cells and the factors they release promote organoid-derived RGC-like cell survival, neuritogenesis, and possibly neuronal maturation.

Cellular and molecular aspects of degenerative disc disease and potential strategies of biological therapy

Back pain is one of the main global health problems with a high level of prevalence and patients’ disability. In most cases, it is associated with degenerative spine damage (degenerative disc disease), dorsopathy, discopathy (M51 and M53 according to the International Classification of Diseases, 10th revision), affecting all levels of the intervertebral disc (IVD) (cytological, chemical and biochemical) as a whole as well as biological molecules that regulate homeostasis of the disc intercellular substance (growth factors, pro-inflammatory cytokines, enzymes). A key point in IVD dehydration is that catabolic processes predominate over anabolic ones due to changed gene expression in the corresponding biologically active molecules, disc angiogenesis and neoinnervation of the structures of the fibrous ring and pulpous nucleus. The latter is responsible for chronic pain in patients.Cells supporting homeostasis in nucleus pulpous, chondrocytes, continuously synthesize and restore proteoglycans and hyaluronic acid in nucleus pulpous, restoring shock-absorbing functions of the vertebral-motor segment. Decreased activity and death of chondrocytes in the avascular disc structure is a serious problem for reparative medicine. In accordance with IVD molecular-cellular mechanisms, numerous approaches to treat degenerative disc disease are being developed, each of which, influencing one of the links in the pathogenesis, has a direct or indirect effect on IVD repair.The article describes morphology, pathogenesis and genetics of degenerative disc disease, as well as main modern strategies of biological therapy: tissue engineering, biologically active substances locally used in IVD matrix, including PRP therapy (Platelet Rich Plasma therapy), methods of gene (using the viral vector) and cell therapy, as well as experience in the local use of genetically engineered biological products. Most successful studies are a combination of cell and gene therapy with the use of synthesized matrices.

A Retrospective Study of Stromal Vascular Fraction Cell Therapy for Osteoarthritis.

BackgroundOsteoarthritis (OA) is progressive degenerative damage to articular cartilage. Current therapeutic options are reduced to control the OA-associated symptoms, leaving the degenerative changes to progress until a joint replacement becomes mandatory. Therefore, therapeutic alternatives are warranted to improve the patient’s quality of life. Cell-based therapy is a developing therapeutic modality, showing promising results in the regeneration of injured cartilage and reduction of on-going inflammation within the affected joint. The current retrospective chart review study was aimed to analyze changes in pain and mobility of subjects with OA after stromal vascular fraction (SVF) cell therapy.MethodsThree hundred fifty subjects with hip and knee OA, treated with autologous SVF cells at the Malacky Hospital (Bratislava, Slovakia) in the period from 2015 to 2018, were included in the retrospective chart review study.ResultsSeven days after SVF cell therapy, 45.2% of subjects experienced improved pain levels and mobility. Three, 6, and 12 months after therapy, improvement in pain levels reached 75.3%, 84.4%, and 84.9%, and improvement in mobility reached 75.2%, 84.4%, and 84.9%.ConclusionsOur study of 350 subjects with hip and knee OA showed a significant improvement in pain levels and mobility 3, 6, and 12 months compared to 7 days after autologous SVF cell administration. The treatment demonstrated a strong safety profile with no severe adverse events or complications reported. The results of the study are showing that SVF cell therapy was more effective in subjects with arthritis stage III compared to arthritis stages I, II, and IV.

E4An Ultrastructural Study by Transmission Electron Microscope of Exocrine Pancreatic Cells in Diabetic Rats Treated with Herbal Combination

The current study was designed to investigate the alterations in the ultrastructure of orgenelles and cellular activity of exocrine pancreatic acini of experimentally induced-diabetic rats and to assess the usefulness of herbal combination supplementation in improving the ultrastructure and cellular activity of exocrine pancreas. The number of albino male rats used were 24 which divided into equally 4 groups; group I: control group, group II: alloxan-induced diabetes mellitus (single intraperitoneal dose of alloxan 120 mg/kg for 3 days), group III: herbal combination treatment composed from the extracts of fenugreek seeds (Trigonella foenum-graecum), black cumin (Nigella sativa) seeds, rhizomes of ginger (Zingiber officinale), leaves of olive (Olea europeae), and seeds of ash (Fraxinus ssp). Each rat given 2.5 ml (0.5 ml from each five mixed plant extracts used) for 2 months. group IV: diabetes was induced as group II and treated with herbal combination as group III for 2 months. The processing for investigating by transmission electron microscopy were carried out for all pancreata taken from all groups. There was significant reduction (p<0.05) in mean of FBG levels in diabetic rats treated with herbal combination (group IV) as compared to diabetic control and could revert FBG to normal value compared to negative control The results of examination of semithin and ultrathin sections in diabetic rats revealed many degenerative changes in the exocrine pancreatic tissue in comparison to control group. These degenerative changes can be summarized as disturbances in the arrangement of pancreatic acinar cells and decreased secretory granules in addition to the vacuolation of cytoplasm and pyknotic nuclei were observed in semithin sections. Moreover, degenerated nuclei, vacuolation of cytoplasm, fragmentation of rough endoplasm reticulum and degranulation of the most pancreatic acinar cells were noticed in ultrathin sections. In contrast, the acinar cells of group administrated with herbal combination only had normal ultrastructure, cellular activity, and nuclei, well-developed rough endoplasmic reticulum with abundant zymogen granules. Also, most of the acinar cells retrieved their normal ultrastructure and cellular activity in diabetic group treated with herbal combination and herbal combination could decrease most of the degenerative changes caused by alloxan-induced diabetes. In conclusion, the daily supplementation with this herbal combination to diabetic rat for 2 months could achieving promising effects due to its cytoprotective influence and showed the ability to decreased degenerative damage in the ultrastructure and cellular activity of exocrine pancreatic acini in type 2 diabetic rats.

The Roles of Indian Hedgehog Signaling in TMJ Formation.

The temporomandibular joint (TMJ) is an intricate structure composed of the mandibular condyle, articular disc, and glenoid fossa in the temporal bone. Apical condylar cartilage is classified as a secondary cartilage, is fibrocartilaginous in nature, and is structurally distinct from growth plate and articular cartilage in long bones. Condylar cartilage is organized in distinct cellular layers that include a superficial layer that produces lubricants, a polymorphic/progenitor layer that contains stem/progenitor cells, and underlying layers of flattened and hypertrophic chondrocytes. Uniquely, progenitor cells reside near the articular surface, proliferate, undergo chondrogenesis, and mature into hypertrophic chondrocytes. During the past decades, there has been a growing interest in the molecular mechanisms by which the TMJ develops and acquires its unique structural and functional features. Indian hedgehog (Ihh), which regulates skeletal development including synovial joint formation, also plays pivotal roles in TMJ development and postnatal maintenance. This review provides a description of the many important recent advances in Hedgehog (Hh) signaling in TMJ biology. These include studies that used conventional approaches and those that analyzed the phenotype of tissue-specific mouse mutants lacking Ihh or associated molecules. The recent advances in understanding the molecular mechanism regulating TMJ development are impressive and these findings will have major implications for future translational medicine tools to repair and regenerate TMJ congenital anomalies and acquired diseases, such as degenerative damage in TMJ osteoarthritic conditions.

Galectin-1 exhibits a protective effect against hepatotoxicity induced by dextran sulfate sodium in mice.

Galectin-1 is an important mediator that regulates the T-cell-mediated immune response. It has many other biological functions such as cell growth, immunomodulation, and wound healing. The aim of this study was to reveal the role of galectin-1 on liver morphology, cell proliferation, apoptosis, inflammatory and anti-inflammatory mediators, oxidative stress, and antioxidant system in colitis-mediated hepatotoxicity induced by dextran sulfate sodium (DSS). In the present study, adult mice were divided into four groups: The control group intraperitoneally injected with phosphate buffer saline (I), the group which was orally administered with DSS (II), the control group which was injected with galectin-1 (III), and the group which was given DSS and galectin-1 (IV). DSS administration caused degenerative changes and diffuse necrotic damage, an increase in caspase-3 and cyclooxygenase-2 expression, the levels of lipid peroxidation and tumor necrosis factor-alpha, lactate dehydrogenase, and myeloperoxidase activities, and a decrease in cell proliferation, interleukin-10 levels, and antioxidant system parameters in liver tissues. Treatment of DSS group with galectin-1 reversed these effects and prevented liver damage. This study showed that galectin-1 has proliferative, antiapoptotic, anti-inflammatory, and antioxidant effects against DSS-induced liver injury in mice. It is expected considering all results of this study that galectin-1 may be useful as a protective agent against liver toxicity.

Three-dimensional finite-element analysis of aggravating medial meniscus tears on knee osteoarthritis

BackgroundThe biomechanical change during the medial meniscus damage in the process of knee osteoarthritis has not been explored. The purpose of this study was to determine the effect of aggravating medial meniscus degenerative tear on the progress of knee osteoarthritis through the finite-element simulation method. MethodsThe three-dimensional digital model of a total-knee joint was obtained using a combination of magnetic resonance imaging and computed tomography images. Four types of medial meniscus tears were created to represent the aggravating degenerative meniscus lesions. Meniscectomy of each meniscal tear was also utilized in the simulation. The compression and shear stress of bony tissue, cartilage, and meniscus were evaluated, and meniscus extrusion of the healthy knee, postinjured knee, and postmeniscectomy knee were investigated under the posture of balanced standing. ResultsBased on the results of finite-element simulation, the peak shear principal stress, peak compression principal stress, and meniscus extrusion increased gradually as the meniscus tears’ region enlarged progressively (from 7.333 MPa to 15.14 MPa on medial femur and from 6 MPa to 20.94 MPa on medial tibia). The higher stress and larger meniscus extrusion displacement in all tests were observed in the flap and complex tears. The oblique tears also had a biomechanical variation of stress and meniscus extrusion in the knee joint, but their level was milder. Both the peak value of the stress and meniscus displacement increased after the meniscectomy. ConclusionIn contrast to the damaged hemijoint, the stress applied on the healthy lateral hemijoint increased. The change of biomechanics was more obvious with the aggravation of meniscus injury. The advanced degenerative damage resulted in increasing stress that was more likely to cause symptomatic clinical manifestation in the knee joint and accelerate the progress of osteoarthritis. Moreover, we found that the meniscus injury caused higher stress concentration on the contralateral side of the joint. We also discovered that the meniscectomy can lead to more serious biomechanical changes, and although this technique can relieve pain over a period of time, it increased the risk of osteoarthritis (OA) occurrence. The translational potential of this articleIt is clear that the meniscal lesions can cause osteoarthritic knee, but the biomechanical change during the meniscus damage period has not been explored. We have evaluated the variation of stress during the aggravating medial degenerative meniscus tears and the relationship in the process of knee OA through finite-element simulation. This study does favour to obtain a better understanding on the symptoms and pathological changes of OA. It also may provide some potential directions for the prophylaxis and treatment of OA.

RHEB gene therapy maintains the chondrogenic characteristics and protects cartilage tissue from degenerative damage during experimental murine osteoarthritis

Osteoarthritis (OA) is characterized by cartilage degeneration resulting from hypertrophic changes in chondrocytes caused by altered gene expression. The involvement of Ras homolog enriched in brain (RHEB) in OA regulation is unclear. Human knee articular cartilage samples - were analyzed for structural and biological changes by histology, immunohistochemistry, real time PCR and western blotting. OA-mouse model developed by surgical destabilization of the medial meniscus (DMM) were treated with adenovirus harboring Rheb gene to analyze onset and progression of OA. Histological scoring, immunohistochemistry, and TUNEL assay was performed to assess cartilage damage across the entire joint. Human and mouse OA cartilage is degenerated and has markedly reduced levels of RHEB. Human OA-degenerated chondrocytes (DC) exhibited a fibroblastic phenotype and 80 % of degenerative cartilage were senescent, with higher levels of reactive oxygen species (ROS). Gene expression analysis of DC revealed almost no COL2A1 expression and reduced SOX9 and RHEB expression. Transient transfection of RHEB rescued the DC phenotype and reduced senescence and ROS levels markedly. RHEB overexpression also increased COL2A1 and SOX9 expression. In an OA-mouse model, the Rheb protein level decreased as the severity of OA increased. Ectopic expression of Rheb using adenovirus in mouse-OA cartilage suppressed surgically-induced OA pathogenesis accompanied by modulation of Adamts5, Mmp 13, Col 10, and Col2a1 expression. Rheb induction significantly reduced apoptosis in OA-cartilage. RHEB plays an important role in maintaining the chondrogenic characteristics of chondrocytes, and has potential in preventing progression of OA in the destabilize the medial meniscus (DMM) mouse model of OA.

Lipid Peroxidation Activity and Immune Response in Modeling Inflammatory and Degenerative Damage to the Periodontium of Rats

Lipid Peroxidation Activity and Immune Response in Modeling Inflammatory and Degenerative Damage to the Periodontium of Rats

Molecular Relationships among Obesity, Inflammation and Intervertebral Disc Degeneration: Are Adipokines the Common Link?

Intervertebral disc degeneration (IVDD) is a chronic, expensive, and high-incidence musculoskeletal disorder largely responsible for back/neck and radicular-related pain. It is characterized by progressive degenerative damage of intervertebral tissues along with metabolic alterations of all other vertebral tissues. Despite the high socio-economic impact of IVDD, little is known about its etiology and pathogenesis, and currently, no cure or specific treatments are available. Recent evidence indicates that besides abnormal and excessive mechanical loading, inflammation may be a crucial player in IVDD. Furthermore, obese adipose tissue is characterized by a persistent and low-grade production of systemic pro-inflammatory factors. In this context, chronic low-grade inflammation associated with obesity has been hypothesized as an important contributor to IVDD through different, but still unknown, mechanisms. Adipokines, such as leptin, produced prevalently by white adipose tissues, but also by other cells of mesenchymal origin, particularly cartilage and bone, are cytokine-like hormones involved in important physiologic and pathophysiological processes. Although initially restricted to metabolic functions, adipokines are now viewed as key players of the innate and adaptative immune system and active modulators of the acute and chronic inflammatory response. The goal of this review is to summarize the most recent findings regarding the interrelationships among inflammation, obesity and the pathogenic mechanisms involved in the IVDD, with particular emphasis on the contribution of adipokines and their potential as future therapeutic targets.

Biomechanics of walking before and after surgical treatment of damaged menisci of the knee joint

A significant part of the knee joint (KJ) damages comprise the lesions of its menisci. Both traumatic and degenerative menisci damages are frequent indications for surgical treatment. In the available literature there are a few articles devoted to the study of the KJ function when walking before and after meniscus resection. We have studied the biomechanical changes characteristic of KJ meniscus damage, before and after surgical treatment. The study included 24 patients who were operated on for meniscus rupture of both traumatic and degenerative nature. During the arthroscopic intervention, we performed a meniscus resection within the damaged unstable tissues. In the postoperative period all patients received rehabilitation treatment. The control group included 20 healthy adults (14 males and 6 females). The median age was 29.7 years. The biomechanics of gait was studied: the time of the step cycle, movements in the hip joints (HJ) and KJ in three mutually perpendicular planes and shock loads during walking. The time characteristics of the step cycle remain normal both before and after surgery. The load on the affected limb increases in the postoperative period. The amplitude of movements in HJ and KJ is reduced before treatment and restored after it. KJ meniscus damage does not lead to a significant change in the biomechanics of walking. The recorded parameters of the step cycle do not change, i.e. the existing changes do not affect the time structure; 3 months after surgical treatment on the side of the lesion, shock loads increase to normal values, the amplitude of HJ extension, KJ flexion and rotational movements in it increases. The function of operated KJ was normalized in conditions of walking on a flat surface.

A study on the concentration of heavy metals and histopathological changes in Persian jirds (Mammals; Rodentia), affected by mining activities in an iron ore mine in Iran.

Mining activity constitutes a potential source of heavy metal pollution in the environment. Long-term exposure to heavy metals (e.g., cadmium) has adverse health effects. Rodents frequently serve as bioindicators to monitor the levels of heavy metals in the environment. In the present study, concentrations of 10 heavy metals (Cd, Co, Cr, Cu, Fe, Mo, Ni, Pb, Sb, and Zn) in kidney, liver, and muscle tissue of the Persian jird (Meriones persicus) were evaluated. This is the first study to examine the histopathological changes in Persian jird tissues caused by the bioaccumulation heavy metals. The samples were taken at location that surrounded by Sangan Iron Ore Mine (SIOM) mining activities, in northeastern Iran. The results show that the highest concentrations for the metals were observed in kidney and liver, whereas lowest concentrations were found in muscle of Persian jirds. The concentration of Pb was below the limit of detection. Sex and age were two factors that could explain the different levels of heavy metal bioaccumulation, which affects the concentration of some metals. Adults had significantly higher Cu and Cd levels compared to juveniles. Males bioaccumulated more Zn in their kidneys than females, whereas females bioaccumulated more Fe in their livers. As expected, heavy metals affected various organs of the studied specimens. Hyperemia, hemorrhage, necrosis, and degenerative damage to the epithelial cells of the tubules, the presence of hyaline casts, and in one case, mononuclear leukocyte infiltration, were observed in samples of renal tissue. Hemorrhage and hepatocyte vacuolization were the most common histopathological changes found in samples of hepatic tissue. These effects and the concentrations of heavy metals in the studied specimens indicate the need for monitoring and frequent sampling to evaluate long-term persistent pollutants.

Microendoscopic Decompression for Lumbar Spinal Stenosis With Degenerative Spondylolisthesis: The Influence of Spondylolisthesis Stage (Disc Height and Static and Dynamic Translation) on Clinical Outcomes.

This study was a retrospective subgroup analysis of prospective cohort data. The main objectives of this study were to develop a classification of degenerative spondylolisthesis (DS) and concurrent lumbar spinal stenosis (LSS) based on pathologic stage, and to determine how these subtypes of DS affect outcomes for minimally invasive (MIS) decompression SUMMARY OF BACKGROUND DATA:: DS with LSS is a common clinical scenario, yet there is no consensus on optimal treatment. Natural history of DS is described as early degenerative damage, followed by instability, and eventual restabilization via spondylotic changes. MIS decompression surgery has become increasingly popular, but the effect of DS subtypes on clinical outcomes after MIS decompression is unknown. From 2008 to 2013, all patients who underwent microendoscopic laminotomy for single-level LSS with DS were included. In total, 218 patients (91 male, 127 female individuals) were reviewed. DS pathologic staging was defined as early, advanced, or end stage, based on percent slippage (10% slippage), degree of dynamic instability (3 mm), and disc height. The following variables were evaluated preoperatively and >2 years postoperatively and compared among groups: Japanese Orthopaedic Association (JOA) score, JOA recovery rate, and Visual Analog Scale low back pain. In total, 173 patients were included in final analysis. Final follow-up period was 2.3 years. Average JOA recovery rate was 63.8%. There were no significant differences in JOA recovery and Visual Analog Scale among 3 DS stages (P>0.05). In total, 9.8% of patients required additional spine surgery, with 5% requiring subsequent fusion. All patients who required subsequent fusion were in the advanced stage DS group. Microendoscopic decompression is an effective treatment for patients with DS and concurrent LSS, with only 5% of patients requiring subsequent fusion at over 2-year follow-up, and another 5% requiring revision or adjacent segment decompression. The advanced stage DS group, indicating a >10% anterolisthesis and/or >3 mm of dynamic instability, was more likely to require additional surgery.

C-Reactive Protein, Plasma Amyloid-β Levels, and Their Interaction With Magnetic Resonance Imaging Markers

Background and Purpose- Inflammation is involved in the pathogenesis of large artery atherosclerosis, ischemic stroke, and Alzheimer dementia. However, the role of inflammation in cerebral small vessel disease and neurodegeneration remains poorly understood. We hypothesize that CRP (C-reactive protein) is associated with brain structural changes and may interact with amyloid to produce vascular and degenerative damage. We examined the association of CRP levels with imaging markers of cerebral small vessel disease and neurodegeneration. Furthermore, we studied the association of CRP with plasma Aβ (amyloid-β) levels and their joint effects with imaging markers. Methods- We included 2814 persons (mean age, 56.9 years; 44.8% women) from the Rotterdam Study with complete data on CRP and 1.5 T brain magnetic resonance imaging scans. Aβ levels were measured in a subsample (n=736). Markers of cerebral small vessel disease included lacunes, white matter hyperintensities, microbleeds, and enlarged perivascular spaces. Neurodegeneration was assessed by smaller volumes of gray matter, white matter, and hippocampus. Plasma levels of Aβ1-38, Aβ1-40, and Aβ1-42 were assessed using ELISA. Results- Higher CRP levels were associated with larger white matter hyperintensities volume (β=0.07; 95% CI, 0.00-0.13), increasing lacunar (rate ratios, 1.61; 95% CI, 1.19-2.19), enlarged perivascular spaces (rate ratios, 1.01; 95% CI, 1.00-1.03), and deep/infratentorial microbleeds (rate ratios, 1.30; 95% CI, 1.00-1.69) counts. People with high CRP levels had small gray matter volume. We also found significant interaction between CRP and Aβ such that among persons in higher tertiles of Aβ1-42, a strong association was observed between CRP and lacunar ( P interaction, 0.004), enlarged perivascular spaces ( P interaction, 0.002), and microbleed counts ( P interaction, <0.001). Similarly, among persons in higher tertile of Aβ1-38, a strong association was observed between CRP and microbleed counts ( P interaction, 0.004). Conclusions- Higher CRP levels were associated with subclinical markers of cerebral small vessel disease and neurodegeneration. This effect was augmented by an interaction between CRP and Aβ levels. Future longitudinal studies focusing on joint effects of CRP and Aβ on progression of magnetic resonance imaging markers and cognitive decline are warranted.

Detoxication mechanisms of Radix Tripterygium wilfordii via compatibility with Herba Lysimachia christinae in S180-bearing mice by involving Nrf2.

The combined administration between Radix Tripterygium wilfordii Hook F (LGT) and Herba Lysimachia christinae Hance (JQC) belongs to mutual detoxication compatibility of seven emotions in traditional Chinese medicine (TCM) theory. However, until now, the compatibility detoxication mechanisms remain unknown. The present study was undertaken to observe detoxication mechanisms of LGT through compatibility with JQC in tumor-bearing mice by involving NF-E2-related factor 2 (Nrf2)-mediated antioxidant defenses. In addition, influence of compatibility on antitumor activity was also investigated here. Our results demonstrated that compatibility with JQC administration significantly reversed LGT-elevated serum alanine/aspartate transaminase (ALT/AST) levels and alleviated hepatocytes’ swelling or degeneration damage, and at the ratio 2/1 (LGT/JQC) produced the strongest detoxication effect. Besides, compatibility with JQC administration reversed not only LGT-elevated hepatic malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) but also the LGT lowered GSH, glutathione-s transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and interleukin (IL)-10 levels. Furthermore, compatibility with JQC administration significantly up-regulated protein expression of Nrf2 and mRNA expression of it regulated downstream antioxidant genes such as heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase-1 (NQO1), and glutamate cysteine ligase catalytic subunit (GCLC). In addition, compatibility with JQC further decreased LGT-decreased tumor weight and at the ratio 2/1 (LGT/JQC) also exerted the strongest synergistic effect. Collectively, through compatibility with JQC exerted detoxication effect on LGT-induced hepatotoxicity and the mechanisms could be at least partly attributed to up-regulation of Nrf2 and its downstream signals, thereby enhancing antioxidant defenses, and inhibiting lipid peroxidation, oxidative stress, and inflammation. Additionally, at the ratio 2/1 (LGT/JQC) exerted the strongest effects on both detoxication and synergism.

Comparative Assessment of the Bioremedial Potentials of Potato Resistant Starch-Based Microencapsulated and Non-encapsulated Lactobacillus plantarum to Alleviate the Effects of Chronic Lead Toxicity.

Lead (Pb) is a well-recognized and potent heavy metal with non-biodegradable nature and can induce the oxidative stress, degenerative damages in tissues, and neural disorders. Certain lactic acid bacterial strains retain the potential to mitigate the lethal effects of Pb. The present work was carried out to assess the Pb bio-sorption and tolerance capabilities of Lactobacillus plantarum spp. Furthermore, potato resistant starch (PRS)-based microencapsulated and non-encapsulated L. plantarum KLDS 1.0344 was utilized for bioremediation against induced chronic Pb toxicity in mice. The experimental mice were divided into two main groups (Pb exposed and non-Pb exposed) and, each group was subsequently divided into three sub groups. The Pb exposed group was exposed to 100 mg/L Pb(NO3)2 via drinking water, and non-Pb exposed group was supplied with plain drinking water during 7 weeks prolonged in vivo study. The accumulation of Pb in blood, feces, renal, and hepatic tissues and its pathological damages were analyzed. The effect of Pb toxicity on the antioxidant enzyme capabilities in blood, serum, as well as, on levels of essential elements in tissues was also calculated. Moreover, KLDS 1.0344 displayed remarkable Pb binding capacity 72.34% and Pb tolerance (680 mg/L). Oral administration of both non- and PRS- encapsulated KLDS 1.0344 significantly provided protection against induced chronic Pb toxicity by increasing fecal Pb levels (445.65 ± 22.28 μg/g) and decreasing Pb in the blood up to 137.63 ± 2.43 μg/L, respectively. KLDS 1.0344 microencapsulated with PRS also relieved the renal and hepatic pathological damages and improved the antioxidant index by inhibiting changes in concentrations of glutathione peroxidase, glutathione, superoxide dismutase, malondialdehyde, and activated oxygen species, which were affected by the Pb exposure. Overall, our results suggested that L. plantarum KLDS 1.0344 either in free or encapsulated forms hold the potentiality to deliver a dietetic stratagem against Pb lethality.

Effects of Zanthoxylum piperitum ethanol extract on osteoarthritis inflammation and pain.

Degenerative arthritis, also known as osteoarthritis (OA), is the most common type of arthritis, which is caused by degenerative damage of the cartilage, which primarily protects the joints, leading to inflammation and pain. The objective of this study was to investigate the in vivo and in vitro effects of treatment with ZPE-LR (90% EtOH extract of Zanthoxylum piperitum) on pain severity and inflammation. When using an in vivo OA model MIA (monosodiumidoacetate-induced arthritis) rats, ZPE-LR (100 mg/kg) oral-administratio significantly inhibited MIA-induced change in loaded weight ratio on the left foot, and articular cartilage thickness. To confirm the positive effects on pain relief, acetic acid, heat and formalin-induced pain were remarkably decreased by 50 and 100 mg/kg ZPE-LR oral-administration. Pain related KCNJ6 mRNA expression as well as K + current was increased after ZPE-LR treatment in BV-2 cells. To confirm the positive effects on inflammation, TPA (12-O-tetradecanoylphorbol-13-acetate) induced inflammation measured by mouse ear thickness and biopsy punch weight and TPA-induced iNOS, COX-2 mRNA and protein expression were remarkably suppressed by 50 and 100 mg/kg ZPE-LR oral-administration. In addition, TPA-induced iNOS, COX-2 mRNA level and protein expression were reduced. Acetic acid, heat and formalin-induced pain were remarkably decreased by 50 and 100 mg/kg ZPE-LR oral-administration. We examined in vitro ZPE-LR effects in LPS-induced RAW 264.7 cells. LPS-induced p65 translocation to the nucleus was prohibited by ZPE-LR 100 μg/ml oral administration. Moreover, ROS generation by LPS was significantly inhibited by ZPE-LR 50 and 100 μg/ml treatment. To investigate new ZPE-LR activating mechanisms, the gene fishing method (not a typical term, should probably use PCR based genetic screening) was used. LPS-induced HPRT1 (hypoxanthine phosphoribosyltransferase 1) was decreased by ZPE-LR. However, RPL8 (Ribosomal protein L8) which showed no change in mRNA expression due to LPS, did show increased mRNA levels after ZPE-LR treatment. Our data elucidate mechanisms underlying ZPE-LR and suggest ZPE-LR may be a potential therapeutic agent to modulate osteoarthritis inflammation and pain.

Experimental diabetes induced by streptozotocin in the desert gerbil, Gerbillus gerbillus, and the effects of short-term 20-hydroxyecdysone administration

The present work was aimed at studying the effects of streptozotocin (STZ; 130 mg/kg) in the desert gerbil, Gerbillus gerbillus, and at evaluating the impact of the short-term administration of 20-hydroxyecdysone (20E; 5 mg/kg). We observed that administration of streptozotocin caused a significant increase in plasmatic glucose and a decrease in insulin levels. The plasma lipid profile and liver glycogen content were also altered. The activities of antioxidant enzymes and malondialdehyde (MDA) levels were increased in the pancreatic tissue of STZ-treated gerbils. Moreover, histopathological and immunohistochemical analysis showed degenerative damage in the pancreas with a decline in the percentage area of β-cells. Treatment of STZ-treated gerbils with 20E counteracted metabolic disorders and reduced lipid peroxidation. Histological and immunohistochemical studies showed moderate amelioration in the pancreatic structure. These findings indicate that streptozotocin administration induced experimental diabetes in gerbils and that short-term administration of 20E has beneficial effects in glucose homeostasis in STZ-treated gerbils suggesting that 20E may stimulate surviving β-cells to release more insulin.

Down-regulation of CatSper 1 and CatSper 2 genes by lead and mercury

In the study of the expression of CatSper genes, consideration of the effects of environmental metal toxicity is very important. Therefore, in this study, the effects of lead acetate and mercury chloride exposure on expression of CatSper genes, sperm parameters, histology of testis and prooxidant antioxidant balance (PAB) values of serum were investigated.A total of 28 mice was divided into four groups. The control group did not receive injections. The sham group received normal saline intraperitoneally. Lead and mercury groups were injected 60 and 1.25 mg/kg/daily lead acetate and mercury chloride respectively intraperitoneally for 2 weeks. After 35 days, the sperm analysis and histology of left testis were performed. In addition, serum was obtained to measure the PAB values. The right testis was used for molecular analysis of real-time PCR.Administration with either lead acetate or mercury caused significant damage to the seminiferous tubules as well as a reduction in sperm parameters compared to the control group. The relative expression of CatSper 1 and CatSper 2 in the lead group was lower than that of the control group (−0.01 ± 0.24, −0.007 ± 0.52 vs. 1 ± 0.50, P = 0.34). The relative expression of CatSper 1 and CatSper 2 was significantly lower in the mercury group compared to the control ones (−0.24 ± 2.28, −4.49 ± 4.86 vs. 1 ± 0.50, P = 0.21). PAB values significantly increased in lead or mercury exposed- mice compared to the control ones (0.93 ± 0.17, 1.54 ± 0.17 vs. 0.51 ± 0.11; P ≤ 0.000).The results of this study showed that administration with either lead acetate or mercury chloride caused degenerative damage in seminiferous tubules and reduction in sperm quality and expression of CatSper 1, 2 genes in mice. Therefore, it is possible in infertile men who have had exposure to lead acetate or mercury chloride. Owing to structural similarities, these metals are substitutes for calcium ions and have effects on calcium channels. These cause immobility in sperm by blocking CatSper-specific calcium channels. However, more studies are required to elucidate the mechanism underlying the impact of different doses of heavy metals on CatSper genes expression.

Clinical Evaluation of the Effect of Blueberries Consumption on Chronic Diseases, Illness Prevention and Health Promotion

Background: The ever-growing concern about achieving quality of life and longevity leads scientists to the search of natural wellness resources. Also, prevention of diseases through food is considered as the driving force of the organism. The beneficial effects of superfoods, such as blueberries, on human health are expected to be proved, putting these effects under the microscope. Objective: Evaluating the effect of blueberries consumption in humans, in order to draw relevant conclusions for their beneficial effect and thus develop food policies and launch target in future searches. Methods: Comprehensive review of published studies of the last decade, using keyword combinations which are derived from the available database. Results: Based on the cited studies, that blueberries consumption reduces degenerative damage caused by free radicals, increases the natural killer cells and inflammatory cytokines, and provides evidence for cellular antioxidant defense against DNA damage, playing also an important role in the anti-cancer nutritional preventive treatment. Moreover, the blueberries consumption protects the elderly from neurodegenerative diseases, which are associated with oxidative stress and aging, improves gait performance, vascular function and insulin sensitivity. It also benefits school-age children’s cognitive function. The blueberries consumption also positively influences certain bifidobacterial populations, affects the recovery of visual acuity and operates as a complementary therapeutic factor to reduce the severity of juvenile idiopathic arthritis. Conclusion: The consumption of blueberries is a supplementary function to prevent and cure chronic inflammatory diseases, providing an admirable medical therapy support in order to reduce degenerative damage. However, further studies conducted on larger populations are strongly recommended. Keywords: Blueberries, chronic diseases, complementary therapeutic factor, degenerative damage, human health, Vaccinium myrtillus.